The repair or augmentation of soft tissue, such as soft tissue defects, or contour abnormalities caused by a variety of factors, such as facial defects, acne, surgical scarring or aging, accidents or purely for cosmetic reasons, has proven to be challenging. A number of materials have been used to correct soft tissue defects or augment soft tissue, with varying degrees of success. In the past, liquid silicone was used to correct minor soft tissue defects where minimal mechanical stress was present at the recipient's site. Unfortunately, it appears that liquid silicone from these injections may migrate to distant body parts and cause a variety of physiological and clinical problems. In response to these problems and the misuse of liquid silicone, the FDA at times prohibited the use of liquid silicone in humans.
In the 1970's, reconstituted injectable bovine collagen became available and appeared to be an effective treatment for soft tissue defects. However, over time, the benefits of the collagen treatment have proven to be short-lived; the collagen reabsorbs in two to three months. Additionally, safety measures must be employed with this material to avoid allergic reactions to the bovine proteins in the collagen. To solve these shortcomings, crosslinked collagen has been introduced to extend the effect of treatments to approximately six (6) months. However, allergic reactions may still occur with the cross-linked collagen material and frequent re-administration of the cross-linked material is still required.
U.S. Pat. No. 6,716,251, assigned to Aventis Pharmaceuticals Holdings, Inc., describes the use of an injection implant for filling up wrinkles, thin lines, skin cracks and scars, for reparative or plastic surgery, aesthetic dermatology, and for filling up gums in dental treatment. The implant includes biologically absorbable polymer microspheres or microparticles suspended in a gel. Two polymer families are described as being suitable, the polycaprolactones (and in particular the poly-epsilon-caprolactones), as well as the polylactides (polylactic acids or PLA), the poly-glycolides (polyglycolic acids or PGA) and their copolymers (polylactic-co-glycolic acids or PLAGA).
U.S. Pat. No. 4,938,763, assigned to Atrix Laboratories, Inc., discloses the use of biodegradable polymers as prosthetic implants and controlled-release, drug-delivery systems which can be administered as liquids via, for example, a syringe and needle, but which coagulate or cure shortly after dosing to form a solid. The implants are biodegradable because they are made from biodegradable polymers and copolymers comprising two types of polymer systems: thermoplastic and thermosetting. Examples of thermoplastic systems are polylactides, polyglycolides, polycaprolactones, and polyamides, preferably polylactides, polycaprolactones, and copolymers thereof with glycolide in which there are more amorphous regions to enhance solubility. The polymers used in the thermosetting system are multifunctional polymers which are first synthesized via copolymerization of either DL-lactide or L-lactide with epsilon-caprolactone. The polyol-terminated prepolymers are then converted to acrylic ester-terminated prepolymers, preferably by acylation of the alcohol terminus with acryloyl chloride via a Sohotten-Baumann-like technique, i.e., reaction of acyl halides with alcohols. The acrylic ester-terminated prepolymers may also be synthesized in other ways, such as reaction of carboxylic acids (i.e., acrylic or methacrylic acid) with alcohols, reaction of carboxylic acid esters (i.e., methyl acrylate or methyl methacrylate) with alcohols by transesterification, and reaction of isocyanatoalkyl acrylates (i.e. isocyanatoethyl methacrylate) with alcohols.
Adhesion formation after peritoneal surgery is a major cause of postoperative bowel obstruction, in fertility, and chronic pelvic pain. In addition, adhesion formation can occur after abdominal, gynecological, cardiac, thoracic, spinal, ENT, or orthopedic (e.g. tendon, joint, and knee) surgery. Therefore, a methodology by which adhesion formulation after surgery could be reduced or prevented would be of great benefit in reducing postoperative morbidity.
The most straightforward approach to reducing the incidence of adhesion formation remains physically maintaining the adhesiogenic surfaces apart with a mechanical barrier. For example, U.S. Pat. No. 6,403,655, assigned to Ethicon, Inc., describes a method of preventing adhesion formation between tissues by placing a polyoxaester adhesion prevention barrier between such tissues. Exemplified in the disclosure are a polyoxaester of 3,6-dioxaoctanedioic acid and ethylene glycol, as well as a copolymer of polyoxaester/caprolactone/glycolide.
U.S. Pat. No. 5,644,002 assigned to Ethicon, Inc., describes absorbable polymers and blends of polycondensation polyester and aliphatic polyesters based on lactone monomers, where the polycondensation polyester is the reaction product of diglycolic acid and an alcohol selected from the group consisting of glycerol, pentaerythitol, trimethylolpropane, hydroxyl terminated polyethylene glycols, ethylene glycol, 1,2-propanediol, 1,3-propanediol, 1,4-butylene glycol, dipropylene glycol, 1,5-pentanediol, 1,6-hexanediol, 1,7-heptanediol, and 1,8-octanediol. This reference teaches that the incorporation of hydroxyl terminated poly(ethylene glycol)s in the polycondensation polyester is desirable because it leads to polymers which are useful as adhesion prevention barriers. Additionally, this reference discloses that ultrathin coatings of about 1 to about 1000 microns can be applied to tissue surfaces for the prevention of adhesions. Some compositions of this reference may be used as soft tissue augmentation fillers.
U.S. Pat. Nos. 3,997,512, 4,048,256, 4,076,798, 4,095,600, 4,118,470, and 4,122,129 assigned to American Cyanamid Company, describe biocompatible and absorbable polycondensation polyesters, which are the polycondensation product of diglycolic acid and glycols such as ethylene glycol, diethylene glycol, 1,2-propylene glycol, 1,3-propylene glycol, and the like. Specifically, U.S. Pat. No. 4,095,600 describes a reaction product of (a) about 2 to 50% by weight of the polycondensation polyester and (b) polyglycolic acid, based on the total weight of the polycondensation polyester and polyglycolic acid, to form a self-supporting polymeric film for use, for example, in drug delivery. This reference is silent with respect to use of the composition for adhesion prevention.